Gamma and temperature hardened pharmaceutical devices

ABSTRACT

A system and method for implementing embedded electronics in environments where radiation or extreme temperatures are used is disclosed. Embedded electronics are affixed to various components of a pharmaceutical system, thereby enabling the customer to download pertinent information about the component, such as lot number, date of manufacturer, test parameters, etc. Additionally, these electronics allow an array of functions and features to be implemented, such as integrity tests and diagnostics. The electronics in the pharmaceutical components utilize a technology that is not as susceptible to radiation and extreme temperatures as traditional electronics.

This application claims priority of U.S. Provisional Patent ApplicationSer. No. 61/190,049, filed Jul. 16, 2008, the disclosure of which isherein incorporated by reference in its entirety.

BACKGROUND OF THE INVENTION

The use of electronics in pharmaceutical devices has become prevalent,especially in the management of assets, particularly those applicationsassociated with inventory management. For example, the use of RFID tagspermits the monitoring of the production line and the movement of assetsor components through the supply chain. Additionally, these electronicsallow more functionality to be embedded in the devices. Such functionsas integrity testing, calibration and diagnostics, can now be performedin situ because of the use of these embedded electronics.

To further illustrate one such use of embedded electronics, amanufacturing entity may affix RFID tags to components as they enter theproduction facility. These components are then inserted into theproduction flow, forming sub-assemblies in combination with othercomponents, and finally resulting in a finished product. The use of RFIDtags allows the personnel within the manufacturing entity to track themovement of the specific component throughout the manufacturing process.It also allows the entity to be able to identify the specific componentsthat comprise any particular assembly or finished product.

In addition, the use of RFID tags has also been advocated within thedrug and pharmaceutical industries. In February 2004, the United StatesFederal and Drug Administration issued a report advocating the use ofRFID tags to label and monitor drugs. This is an attempt to providepedigree and to limit the infiltration of counterfeit prescription drugsinto the market and to consumers.

Since their introduction, RFID tags have been used in many applications,such as to identify and provide information for process control infilter products. U.S. Patent RE 39,361, reissued to Den Dekker in 2006,discloses the use of “electronic labels” in conjunction with filteringapparatus and replaceable filter assemblies. Specifically, the patentdiscloses a filter having an electronic label that has a read/writememory and an associated filtering apparatus that has readout meansresponsive to the label. The electronic label is adapted to count andstore the actual operating hours of the replaceable filter. Thefiltering apparatus is adapted to allow use or refusal of the filter,based on this real-time number. The patent also discloses that theelectronic label can be used to store identification information aboutthe replaceable filter.

U.S. Pat. No. 7,259,675, issued to Baker et al, in 2007, discloses aprocess equipment tracking system. This system includes the use of RFIDtags in conjunction with process equipment. The RFID tag is described ascapable of storing “at least one trackable event”. These trackableevents are enumerated as cleaning dates, and batch process dates. Thepublication also discloses an RFID reader that is connectable to a PC oran internet, where a process equipment database exists. This databasecontains multiple trackable events and can supply information useful indetermining “a service life of the process equipment based on theaccumulated data”. The application includes the use of this type ofsystem with a variety of process equipment, such as valves, pumps,filters, and ultraviolet lamps.

RFID tags are but one use of embedded electronics as used inpharmaceutical devices. U.S. Pat. No. 7,048,775 issued to Jornitz et alin 2006, discloses a device and method for monitoring the integrity offiltering installations. This publication describes the use of filterscontaining an onboard memory chip and communications device, inconjunction with a filter housing. The filter housing acts as amonitoring and integrity tester. That application also discloses a setof steps to be used to insure the integrity of the filtering elementsused in multi-round housings. These steps include querying the memoryelement to verify the type of filter that is being used, its limit data,and its production release data.

Other patent applications have also disclosed the use of embeddedsensors to aid in diagnostics or in situ integrity tests.

Despite the improvements that have occurred through the use of embeddedelectronics in pharmaceutical devices, there are additional areas thathave not been satisfactorily addressed. For example, to date, embeddedelectronics and RFID tags cannot be employed in environments thatrequire or utilize radiation. This is due to the fact that mostelectronic devices, and particularly memory storage devices, cannotwithstand radiation. When subjected to radiation, specifically gamma andbeta radiation, the contents of these memory elements are corrupted,thereby rendering them useless in this environment. Additionally,certain other electronic components, such as integrated circuits, failwhen subjected to radiation. The most common failure mode is a conditioncommonly referred to as “latchup”. However, there are a number ofapplications, such as, but not limited to, the drug and pharmaceuticalindustries, where radiation of the system is a requirement. Furthermore,many electronic components cannot withstand temperature extremes, suchas temperatures above 125° C. or below −55° C. These extremetemperatures are used in the pharmaceutical industry to sterilizematerials, and to store finished product. Therefore, it would beextremely beneficial to these industries and others, to have embeddedelectronics that could withstand radiation and/or extreme temperatureranges without data loss or corruption.

SUMMARY OF THE INVENTION

The shortcomings of the prior art are overcome by the present invention,which describes a system and method for implementing embeddedelectronics in environments where radiation or extreme temperatures areused. Embedded electronics are affixed to various components of apharmaceutical system, thereby enabling the customer to downloadpertinent information about the component, such as lot number, date ofmanufacturer, test parameters, etc. Additionally, these electronicsallow an array of functions and features to be implemented, such asintegrity tests, sensing of various parameters such as temperature, pH,conductivity, pressure and the like and diagnostics. The electronics inthe pharmaceutical devices utilize a technology that is not assusceptible to radiation and extreme temperatures as traditionalelectronics.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a cross-section of a traditional semiconductor substrate;

FIG. 2 shows the phenomenon that causes latchup in the substrates ofFIG. 1;

FIG. 3 shows a cross-section of a Silicon on Insulator (SOI) substrate;

FIG. 4 shows a block diagram of a sensor;

FIG. 5 shows a cross-section of an ISFET;

FIG. 6 a shows one orientation of a bag and attached semiconductor;

FIG. 6 b shows a second orientation of a bag and attached semiconductor;and

FIG. 7 shows a heater used with a SOI substrate in accordance with oneembodiment.

DETAILED DESCRIPTION OF THE INVENTION

The use of miniature and embedded electronics has become more and moreprevalent. However, in certain applications, their use is limited, ornot possible. For example, any environment in which the electronics mustbe subjected to radiation will corrupt or destroy the physical device,or may alter the state of the device. Therefore, devices that are gammaor beta irradiated, such as pharmaceutical components, or subject tox-rays, such as devices that pass through airport security systems,currently cannot easily utilize electronic circuits. Thus, products usedin these environments must find alternative solutions. For example, insome cases, the electronics are eliminated and a simple barcode isaffixed to the device, and a database is used to store and retrieve thepertinent information associated with that barcode. In other words, thememory element of the tag is literally removed and kept elsewhere. Whilethis allows the data associated with the device to be saved andretrieved, it requires computer access and a remote database forstorage. This solution is further complicated when the devicemanufacturer and the device user both want to access and update theassociated information. Such an arrangement requires joint access to thedatabase, which may be difficult or impossible due to the need forconfidentiality and data protection.

A second solution involves affixing the embedded electronics at a pointin the process after the irradiation of the device. For example,pharmaceutical components are often subjected to gamma or betaradiation. Application of the electronic devices after this step canbypass the memory corruption and circuit malfunction issues describedabove. However, data associated with that component which was createdbefore the radiation step must be somehow saved and associated with theappropriate component, so that the later affixed electronics containsall of the required information. Additionally, the electronic devicemust itself undergo some sterilization process before it can be affixedto the pharmaceutical device.

A third solution is to prohibit the use of radiation with the device.Thus, users must find an alternate approach to achieve the resultssought by irradiating the device (such as high temperature steamsterilization). However, sterilization, such as by autoclave, requirestemperatures typically in excess of 145° C. Military grade integratedcircuits, which are more costly than standard commercial gradeequivalents, are typically only rated to 125° C. Thus, steamsterilization also potentially can damage the electronics. Obviously,none of these solutions is optimal.

At the root of the problem is the inability for a traditionalsemiconductor device to withstand sterilization, such as by gamma orbeta radiation or steam sterilization. This is a very well knownproblem, and affects all types of CMOS semiconductor devices, includingtransistors, memory circuits, amplifiers, power conversion circuits, andanalog/digital and digital/analog converters. FIG. 1 shows the typicalstructure for a CMOS device. The N channel MOSFET 100 comprises a N-typesource 101 separated from an N-type drain 102. The gate 103 is locatedbetween these two N-type regions. The substrate 104 around the MOSFET isp-type. The P channel MOSFET 110 comprises a P-type source 111 separatedfrom a P-type drain 112. The gate 113 is located between these twoP-type regions. The substrate around the MOSFET is n-type moat or well114. When exposed to radiation, these CMOS devices typically fail insuch a way that both the NMOS transistor 100 and its complementary PMOStransistor 110 both turn on, effectively creating a SCR 200 (siliconecontrolled rectifier) or thyristor. These devices are essentiallyN—P—N—P devices, which, once turned on, can only be turned off by theremoval of power from the device. Typically, the SCR is created betweenthe p-drain 112, n-moat 114, p-substrate 104 and n-drain 102 of theadjacent transistor, as shown in FIG. 2. Thus, the activation of thisSCR creating a short circuit between the power rails of the CMOS device,which persists until the power is removed from the device. Although thisproblem most often occurs between power rails, other short circuitswithin the device are also possible. Failure to mitigate this failurecan lead to permanent damage.

Other semiconductor fabrication techniques are known to exist. One suchtechnique is known as Silicon-on-Insulator (or SOI). SOI fabrication hasbeen in use for about 10 years. Companies, such as Honeywell andCissoid, have commercialized circuit components necessary to assemblewireless communication devices as well as basic sensor circuits andamplifiers. Typically, integrated circuits made using SOI techniques areresistant to junction temperatures up to 225° C., well in excess ofcurrent military standards available for traditional CMOS devices. Forexample, traditional integrated circuits are typically specified for twomaximum temperatures; operational and storage. Most standard integratedcircuits have a maximum storage temperature of 150° C., and a maximumoperating temperature of 125° C. In contrast, SOI based integratedcircuits are commonly rated at 225° C. operating temperature.

In contrast to traditional semiconductors, insulating material 300, suchas silicon dioxide (SiO₂), aluminum oxide (Al₂O₃) or other suitablematerials, separates the various transistors from one another and fromthe bulk substrate 330. FIG. 3 shows a cross-section of a typical SOIdevice. Note that the presence of the insulating material 300 betweenthe transistors 310,320 prohibits the formation of the SCR devicedescribed above, thereby mitigating the possibility of latch-up in thesedevices. In addition, the insulating material isolates the transistors310,320 from the doped substrate 330.

As stated above, pharmaceutical devices need to be sterilized. The mostcommon forms of sterilization include gamma or beta radiation, and hightemperature steam sterilization, both of which are impossible withtraditional semiconductor devices.

Currently, the pharmaceutical industry is pursuing the use of disposablecomponents. Typically, these parts are manufactured by thepharmaceutical company and then shipped to the customer. Often, thecustomer assembles these disposable components into a complete system,which they may then sterilize before use. Such disposable systemsinclude the Mobius® line of products manufactured by MilliporeCorporation.

Many of these disposable products benefit because of the advantageslisted above. For example, through the addition of embedded electronics.For example, RFID tags can be read and rewritten by the manufacturerand/or customer to allow improved inventory processes. Based on this, itis possible to develop a sophisticated pharmaceutical asset managementsystem. In one embodiment, the pharmaceutical components, such asfiltration devices, hoses and the like, have a remotely readable tagaffixed to them, such as an RFID tag. This tag contains device specificinformation, such as, but not limited to device specific information(such as serial number, date of manufacture, etc.), devicespecifications (such as upper and lower pressure limits), and devicetest parameters. Customers could use this information in a variety ofways. For example, an automated instrument setup and calibrationprocedure can be established. By using an RFID or equivalent reader, thecustomer could determine calibration values, upper and lower limits,units of measure and/or the data exchange protocol.

This semiconductor technique can also be used to create other embeddedelectronic components that can withstand sterilization, such aspressure, temperature and concentration sensors. It is desirable to usesensors to measure fluid conditions, such as temperature, pressure andflow rate. It is also desirable to measure fluid components, such as byusing a chemical or concentration sensor. The use of some of these typesof sensors is described in U.S. patent application Ser. Nos. 11/402,737,11/402,437, and 11/402,438, the disclosure of each is herebyincorporated by reference. In these cases, information obtained by thesensors can be stored in embedded memory and read by the customer at alater time. Alternatively, the sensor data can be transmitted wirelesslyto a remote transmitter or receiver.

Sensors 400 are typically made up of a number of subcomponents, as shownin FIG. 4. There is a sensor head 410, which is the portion of thesensor that converts the physical characteristic, such as pressure ortemperature, to an electrical signal. This signal can be a voltage, acurrent, a resistance, or any other electrical quantity. The sensor bodyis typically made up of a number of subcomponents, such as a signalprocessing unit 420, an analog to digital converter 430, a transmitter440 and a power circuit 450.

The output from the sensor head may be passed to a signal processingunit 420. This unit 420 may perform a number of different functions. Forexample, this unit 420 may scale the incoming signal to change the inputrange into a different output range. For example, an incoming signal maybe in the range of 0-100 mV, whereas the desired output is between 100mV and 1V. The signal processing unit 420 would translate and scale theincoming voltage to achieve the desired output range.

Alternatively, the signal processing unit 420 may add compensation forthermal drift or other variables. For example, a pressure sensor mayexperience an offset based on the ambient temperature. The signalprocessing unit 420 can compensate for such an error.

In addition, the signal processing unit 420 may adjust the receivedsignal based on known process variation. For example, devices may varyfor each production lot. This variation may be determined by a tester,which then records the required compensation value in the signalprocessing unit 420. This value may be added to the output, or may be ascaling factor.

Additionally, the signal processing unit 420 may include means forcalibration. In this case, the signal processing unit 420 may includemeans to test the process variation and thermal drift. It then performsa calibration test to determine these factors and uses them toappropriately adjust the received electrical signal.

A third subcomponent of a sensor may be an analog to digital converter430. Typically, the sensor head 410 produces an analog output, as avoltage, current or resistance. This output may need to be converted toa digital value. This is typically accomplished through the use of ananalog to digital converter 430. This analog to digital converter 430may receive the output of the signal processing unit 420. Alternatively,it may receive the output of the sensor head 410 and supply a digitalvalue to the signal processing unit 420. In a third embodiment, theanalog to digital converter 430 is located within the signal processingunit 420 and converts the signal after unit has been partiallyprocessing by the signal processing unit 420.

A fourth subcomponent is a transmitter 440. In some embodiments, thetransmitter 440 is simply a wire, which connects the sensor componentsto an external reader. In other embodiments, the transmitter 440 may bewireless. A wireless transmitter may utilize any protocol, and thedisclosure is not limited to any particular embodiment. For example,protocols such as Zigbee, 802.15.1, 802.15.4, RFID, Bluetooth® andothers, are suitable for this application.

A fifth subcomponent of a sensor 400 is the power circuit 450. Thiscircuit 450 provides the required power to the rest of the sensor 400.In some embodiments, a battery is used as the energy source. In otherembodiments, wireless induction is used to supply energy to the sensor.In addition to supplying energy, the power circuit 450 transforms thatenergy into the required voltages, typically through the use ofrectifiers, zener diodes, capacitors, and other components.

In some embodiments, as is described in more detail below, the abovedescribed sensor 400 is at least partially made using SOI technology.For example, in some embodiments, the entire sensor is made using SOItechnology. In other embodiments, only certain subcomponents are madeusing SOI technology.

For example, in some embodiments, the signal processing unit 420, whichmay include integrated circuits, is made using SOI technology.

In other embodiments, the sensor head 420 is made using SOI technology.For example, ISFETs can be used in the creation of concentrationsensors. These ISFETs utilize drain and source regions analogous tothose found in a MOSFET. FIG. 5 shows an ISFET 500 made using SOItechnology. Like traditional MOSFETS, the ISFET has an n-type drainregion 510 and an n-type source region 520. Both regions are locatedwithin a p-type substrate 530, such as silicon. An insulator 540 is thenlayered on top of the p-type silicon 530, the source 520 and the drain510, leaving only a small area on the source and drain regions forconnection to the metal contacts 550. The metal gate traditionally usedfor a MOSFET is replaced by an electrode 560 spaced apart from thedevice. The ions in the solution 570 provide the electrical path fromthe electrode 560 to the device. Thus, the concentration of electronsdetermines the strength of that electrical path, and therefore theamount that the FET is enabled.

Other examples of a sensor head using SOI technology are the use of LEDsor photodiodes. These LEDs can be used to detect concentration densitywhen used with fluorescent materials, and can also be made using SOItechnology.

Additionally, SOI technology is suitable for other devices, includingamplifiers, analog-to-digital converters, digital-to-analog converters,digital logic, radio frequency components, power conversion circuitryand memory devices.

Finally, the ability to utilize a remotely readable asset management tagis beneficial for pharmaceutical consumables, such as filters, bags,tubes and process instruments. Currently, the pharmaceutical industry isexploring the use of disposable technology. In this scenario, thecustomer could configure their required system using at least somedisposable components (such as filters, bags, hoses, etc). This allowsthe customer to customize their configuration as necessary and alsoeliminates the costly cleaning operations that must currently beperformed. To improve the efficiency and predictability of usingdisposable components, RFID tags can be affixed to these components.Such tags allow for the wireless automated identification of components,including such information as catalog number, serial number, and date ofmanufacture. These tags also allow a secure automated method oftransferring unit specific specification to the customer as noted above.Using the information contained within these tags, a GAMP compliantmethod of transferring unit specific test procedure information to anautomated integrity tester can be created. The semiconductor devicesdescribed above are beneficial in this application, since thesedisposable components must be irradiated to insure sterilization.Furthermore, in addition to storage and wireless communications that canbe provided by RFID tags, other functions are also possible given theuse of SOI technology.

There are various applications where this SOI technology would bebeneficially employed. Currently, there are some disposablepharmaceutical components that employ sensors. Due to the issuesassociated with sterilization described above, many separate the sensorinto two connectable portions; a sensor head and a sensor body, whichcontains the remaining subcomponents. The sensor head contains a minimalamount of complexity and is typically designed in such a way so as to beable to withstand radiation or high temperature. The sensor bodyincludes the electronics required to control the inputs to the sensorfield and to convert the output from the sensor head into a meaningfulresult. These two components are typically connected via leads, such aswires, and are connected after the sterilization process is completed.

The use of SOI technology allows for much improved and more convenientimplementation of electronics in sterilized pharmaceutical components.For example, in some embodiments, the sensor head is very sensitive andrequires individualized calibration to insure proper readings. Forexample, an analog output from a sensor head may be related to thetemperature by a particular equation, wherein the coefficients of thatequation are unique to the sensor head. By calibrating the sensor headand storing those values proximate to the sensor head, the sensor headcan now be used with a generic sensor body without any additionalcalibration required. Storing these calibration values proximate to thesensor head requires that the storage device be capable of withstandingsome type of sterilization process. Memories manufactured using the SOItechnologies can be integrated into the sensor head, allowing calibratedsensors to be employed.

In a second embodiment, the sensor head and sensor body are incorporatedinto a single self-contained component. This self-contained sensorincludes the previously described sensor head. As described above, italso includes a power conversion/generation circuit, which generatespower for the device, preferably from radiated electromagnetic fields.The sensor also includes the circuitry necessary to convert the analogoutput from the sensor head into a digital value, the logic required toconvert that value to an appropriate computer usable result, and atransmitter to deliver that result, preferably wirelessly to an externaldevice. If all of these components are manufactured using SOI, theentire sensor can be sterilized without fear of damage or degradation.

As mentioned above, electronic devices using SOI technology canwithstand gamma or beta radiation. To increase the amount of radiationthat the electronic device can withstand, it may be possible to changethe orientation of the device during the sterilization process.Typically, gamma rays are directed predominantly along one axis. Forexample, assume that the gamma rays are moving in the Z axis. Typically,the item to be sterilized, such as a pharmaceutical bag, is placed suchthat its maximum surface area is positioned perpendicular to the flow ofgamma rays. FIG. 6 a shows gamma rays 600 flowing in the Z axis. Theitem to be sterilized 610 and the attached semiconductor device 620 arepositioned so as to maximize the surface area impacted by the gamma rays600. While this orientation is best for the item to be sterilized 610,it subjects the semiconductor device 620 to high levels of radiation.

To reduce these levels of radiation, the semiconductor device 620 can beoriented such that its cross-section (as viewed in FIG. 3) isperpendicular to the flow of gamma rays (such as in the XY plane).Stated another way, the maximum surface area of the semiconductor device620 is oriented so as to be coplanar to the direction of the gamma rays,as shown in FIG. 6 b. In this way, a minimal surface area is susceptibleto being impacted by the rays. Other orientations are also possible,where the cross-sectional exposure of the electronic device is not atits maximum. However, the item to be sterilized 610 still exposes alarge cross-section to the gamma rays 600.

Other techniques may also be used to reduce the effect of gamma or betaradiation on these electronic devices. In some embodiments, a SOI devicemay be temporarily disabled or affected by the exposure to radiation.Reconditioning, by applying heat or simply allowing time to elapse, maybe an effective method to restore the functionality of the device. Inone embodiment, after the device is sterilized, it is not used for apredetermined period of time to allow it to recondition itself. In asecond embodiment, after the electronic device is sterilized, it issubjected to heat to recondition it. In a further embodiment, a smallheater may be installed near the semiconductor device that can beactivated after exposure to radiation. FIG. 7 shows an example of such aheater 710. For example, the heater 710 may consist of a small coiloriented around the semiconductor device 700. The coil can receiveinduced electromagnetic waves, which it then converts to current. Thiscurrent is used to create heat, which is used to recondition thesemiconductor device 700. After exposure to radiation, this heater 710can be activated, which supplies localized heat to the semiconductordevice 700, allowing it to recondition itself.

In addition to the benefit of withstanding sterilization, thesesemiconductor devices can also operate at high temperature ranges.Therefore, it is also possible to have these sensors functional during ahigh temperature steam sterilization procedure. Thus, in situtemperature measurements can be made during sterilization orautoclaving, which allows the operator to verify that the sterilizationtemperature ranges and profiles conform to required values. In contrast,the actual temperature profile of a hot steam sterilization cyclecurrently cannot be monitored in situ.

In addition to withstanding high temperatures, it is also believed thatSOI technology is more tolerant of extremely low temperatures, such asmuch less than −55° C. The ability of a semiconductor material toconduct is proportional to the dopant level and the base energy level,or thermal state. Typically semiconductor devices are doped to operatewithin the common industrial temperatures, −55 to +85 C. Increasing thetemperature of the semiconductor device will increase the ability forthe device to conduct or change states. However, at lower temperatures,the energy required to excite the transistor may exceed the maximuminput energy and therefore standard devices will not operate reliablybelow −55° C. SOI can more reliably operate at lower temperatures thanstandard semiconductor devices because less input energy is lost toparasitic leakage to adjacent devices.

This feature can also be advantageous exploited by pharmaceuticalcomponents. For example, many pharmaceutical products are stored insub-freezing environments. Furthermore, the temperature profile of thedrug as it is being frozen is critical to maintaining the propermolecular and crystalline structure. A temperature sensor that is ableto operate at these frigid temperatures would allow the operator tomonitor the temperature as the product is being frozen to verify thatthe proper temperature profile was followed.

In one embodiment, the temperature sensor records the temperature atfixed intervals and stores these values in an internal memory. At alater time, these stored values can be retrieved by an external devicethat compares the stored values to acceptable temperature profiles. Inanother embodiment, the temperature sensor transmits these values to anexternal device, which monitors the temperature of the product as it isbeing frozen. The transmission can be by wire or wirelessly as describedabove. The external device can then insure that a proper temperatureprofile was followed.

This procedure is not possible today. Rather, freezers are calibratedand then products frozen in that freezer unit are assumed to havefollowed the profile exhibited during calibration. Therefore, this newapproach would allow the operator to insure that each product wassubjected to a proper freezing profile, since the temperature versustime data would be attainable for each individual product.

Similarly, this technique can be used to monitor and verify the thawingprocess. As the frozen product is thawed, its temperature can berecorded by the temperature sensor, as described above. The thawingcontinues until the product reaches its desired use temperature. Thecollected temperature values can then be compared to a proper oracceptable temperature profile to insure the quality of the product.

This technique can also be used to calibrate the freezing profile of thefreezer itself. For example, a freezer is calibrated using thermocouplewires that are thread into the interior. Due to the freezers design withinsulation and sealed enclosure, routing the thermocouples to thepreferred locations within the interior can be complicated and timeconsuming. A device that can wireless communicate through the closure orportals of the freezer may be used to allow temperature to be measuredwith the enclosure.

Silicon on Insulator (SOI) technology is also believed to be moreresistant to magnetic fields, especially alternating magnetic fields.This is believed to be true for several reasons. First, SOI transistorscan hold their state more effectively and efficiently to reduce theeffects of induced currents from the AC field. Second, SOI transistorshave less leakage, therefore they will be less susceptible to drainingthe transistors in an excited state. Such an environment may beencountered in various applications, For example, in the pharmaceuticalindustry, magnetically levitated mixer heads are often used, such as inthe Mobius® Mix 100, 200 and 500 disposable mixer systems available fromMillipore Corporation of Billerica, Mass. These systems use a magneticdrive on the outside of the mixing container to remotely drive amagnetic impeller within the container in order to mix its contentseither as a straight industrial mixer or as a bioreactor. The use of SOItechnology will allow electronics to be placed in closer proximity tothis magnetic field source.

Perhaps the most interesting application of this technology is indisposable products for the biopharmaceutical or medical industry whereone or more of these conditions are used on the same product over itslife time. Having electronics that are capable of working in any or allof these conditions would be exceedingly useful to the operator. Forexample, a sample bag used on a disposable bioreactor, can have one ormore electronic devices, for example a RFID or other wirelesscommunication and memory storage device. One such system is taught bycopending application WO 2009/017612. Having electronics of the SOItype, one can form the sampler bag and attach a wireless communicationsand memory device and then gamma or beta sterilize it for shipping,storage and use by the customer. Data relating to the lot number, dateof manufacture, use restrictions and the like can be safely added beforegamma or beta sterilization and read after gamma or beta sterilization.One or more trackable events such as the date of use, the location ofuse, operator, sample taken etc can be added to the memory by the useras a paperless record keeping system and may interface with its GoodManufacturing or Good Laboratory practices systems such as a LIMSsystems. The sample may then be frozen as a retain and the SOI basedelectronics will allow it to be safely stored at those temperatures andthawed at a later date with its memory and stored data intact.

Similar applications apply to the medical field where blood or othercomponents can be added to gamma or beta sterilized containers andstored at low temperatures until needed. Likewise, retains or medicalsamples such as biopsies could be handled in the same manner and yieldthe same satisfactory results.

1. A method of creating a sterile component, having embeddedelectronics, comprising: manufacturing an electronic device usingSilicon on Insulator (SOI) technology; affixing said electronic deviceto said component; and sterilizing said component by subjecting saidcomponent to gamma or beta radiation.
 2. The method of claim 1, whereinsaid component is selected from the group consisting of filters, bags,tubes and process instruments.
 3. The method of claim 1, wherein saidelectronic device comprises wireless communication means.
 4. The methodof claim 3, wherein said means comprises RFID.
 5. The method of claim 3,wherein said means comprises the communication protocol described inIEEE 802.15.4.
 6. The method of claim 3, wherein said means comprisesthe communication protocol described in IEEE 802.15.1.
 7. The method ofclaim 1, wherein said electronic device is a sensor adapted to convert aphysical characteristic to an electric signal, selected from the groupconsisting of fluid condition sensors, including pressure sensors,temperature sensors, and flow rate sensors, and fluid component sensors,including chemical sensors and concentration sensors.
 8. The method ofclaim 7, wherein said sensor comprises a sensor head, and said sensorhead is manufactured using SOI technology.
 9. The method of claim 7,wherein said sensor comprises a signal processing unit, and said signalprocessing unit is manufactured using SOI technology.
 10. The method ofclaim 1, wherein said radiation is transmitted substantially along onedirection, and said electronic device is oriented so as not to maximizeits surface area exposed to said radiation.
 11. The method of claim 1,further comprising the step of reconditioning said electronic deviceafter exposure to said radiation.
 12. The method of claim 11, furthercomprising attaching a heater near said electronic device and whereinsaid reconditioning comprises activating said heater subsequent to saidexposure to said radiation.
 13. The method of claim 1 further comprisingthe step of reconditioning said electronic device after exposure to saidradiation wherein the step of reconditioning said electronic device isselected from the group consisting of keeping the device shut off for apreset period of time and heating the electronic device.
 14. A method ofcreating a sterile component for pharmaceutical or medical use havingembedded electronics, comprising: manufacturing an electronic deviceusing Silicon on Insulator (SOI) technology; affixing said electronicdevice to said component; and sterilizing said component by subjectingsaid component to high temperature steam sterilization.
 15. The methodof claim 14, wherein said component is selected from the groupconsisting of filters, bags, tubes and process instruments.
 16. Themethod of claim 14, wherein said electronic device comprises wirelesscommunication means.
 17. The method of claim 14, wherein said meanscomprises RFID.
 18. The method of claim 14, wherein said means comprisesthe communication protocol described in IEEE 802.15.4.
 19. The method ofclaim 14, wherein said means comprises the communication protocoldescribed in IEEE 802.15.1.
 20. The method of claim 14, wherein saidelectronic device is a sensor adapted to convert a physicalcharacteristic to an electric signal, selected from the group consistingof fluid condition sensors, including pressure sensors, temperaturesensors, and flow rate sensors, and fluid component sensors, includingchemical sensors and concentration sensors.
 21. The method of claim 20,wherein said sensor comprises a sensor head, and said sensor head ismanufactured using SOI technology.
 22. The method of claim 20, whereinsaid sensor comprises a signal processing unit, and said signalprocessing unit is manufactured using SOI technology.
 23. The method ofverifying the temperature profile of a pharmaceutical or medical productas it is being brought to its desired storage temperature, comprising:a. Affixing a temperature sensor to a container or carrier for saidproduct, wherein said temperature sensor is constructed from electronicdevices manufactured using SOI technology; b. Placing said product intoa temperature chamber adapted to bring said product to said desiredstorage temperature; c. Using said temperature sensor to record aplurality of temperature measurements as said product is brought to saiddesired temperature; and d. Comparing said plurality of temperaturemeasurements to an acceptable temperature profile.
 24. The method ofclaim 23, wherein said temperature sensor records temperatures at fixedintervals.
 25. The method of claim 23, wherein said temperature sensortransmits said plurality of temperature measurements to an externaldevice before said comparison is performed.
 26. The method of claim 23,wherein said measurements are transmitted wirelessly.
 27. The method ofclaim 23 further comprising the steps of (e) bringing the product backto a desired use temperature; (f) Using said temperature sensor torecord a plurality of temperature measurements as said product isbrought back to its desired use temperature; and (g) Comparing saidplurality of temperature measurements to an acceptable temperatureprofile.